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TL;DR
ESA's protective effects were mediated by Nrf2-dependent antioxidant, anti-inflammatory, and hypolipidemic mechanisms.
Saudi Journal of Biological Sciences · 6 authors, 3 centres
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ESA's protective effects were mediated by Nrf2-dependent antioxidant, anti-inflammatory, and hypolipidemic mechanisms.
This preclinical study investigated the protective effects of esculeoside A (ESA), a tomato-derived steroidal glycoside, against streptozotocin (STZ)-induced type 1 diabetes-associated reproductive toxicity in male rats. The STZ-diabetic model was validated by documented loss of body mass, polydipsia, increased food consumption, elevated fasting glucose, and reduced fasting insulin. Diabetic rats exhibited reduced testicular weight, damaged seminiferous tubules and Leydig cells, reduced sperm count, abnormal sperm morphology, lower testosterone, FSH, and LH levels, and inability to impregnate normal female rats. ESA treatment improved fertility index, testicular morphology, sperm parameters, and hormonal levels without significantly altering body weight, food intake, glucose, or insulin levels. ESA attenuated hyperlipidemia, reduced lipid peroxidation, increased antioxidant concentrations, and suppressed NF-κB/TNF-α/IL-6 inflammatory axis activation in testicular tissue. These effects were attributed to Nrf2-dependent mechanisms including upregulation of GSH and enzymatic antioxidants and repression of NF-κB.